MTHFR gene testing

MTHFR gene testing

PRACTICE POINT

There is no substantial evidence to support the use of methylenetetrahydrofolate reductase (MTHFR) gene testing in routine clinical practice. Knowledge of MTHFR gene status is unlikely to change patient management.

What do I need to know?

The MTHFR gene is involved in processing amino acids, specifically in relation to folate metabolism.

There are two variants in MTHFR associated with mildly increased levels of homocysteine in the blood (p.Cys677Thr and p.Ala1298Cys). These variants are common in the general population with around 65% of people having at least one of these.

MTHFR gene testing is promoted by some complementary and alternative practitioners to investigate infertility, recurrent pregnancy loss and risk of particular diseases. However:

  • There is no significant evidence of a causal link between MTHFR gene variants and particular diseases 
  • MTHFR status does not alter the recommendation that women who are planning a pregnancy or those in the first trimester of pregnancy take folic acid supplements to reduce the risk of neural tube defects

Patients can obtain MTHFR gene testing through private providers at their own expense.

There is no indication to refer the patient to genetics services. Given the lack of clinical utility, some genetics service providers are no longer accepting patient referrals for consultations in relation to MTHFR.

Note that other variants in MTHFR can lead to marked increase in homocysteine (homocystinuria) and testing for this condition differs to that outlined above for the two mild variants.

How can I manage MTHFR gene testing in general practice?

Advising patients who are considering MTHFR gene testing

The following points may be useful to raise in a discussion with patients who are interested in ordering a MTHFR gene test:

  • MTHFR gene testing is not recommended because:
    • many people have one or both MTHFR gene variants (Cys677Thr and/or p.Ala1298Cys)
    • there is a lack of strong scientific evidence to show that having one or both of these common MTHFR gene variants causes particular health problems
    • there are no evidence-based treatments that will improve the health of a patient with one or both of the common MTHFR gene variants
  • There is an association between the presence of MTHFR gene variants and mildly increased homocysteine levels; however
    • while mild elevation in homocysteine was once thought to increase risk of blood clots (thrombophilia), cardiovascular disease (CVD) and recurrent pregnancy loss, recent studies have found that this is not the case
    • many other factors also increase homocysteine (ie diet, lifestyle, other gene variants). A person can reduce their risk of disease by following a healthy, balanced diet and avoiding well-known risk factors such as smoking and being overweight
    • having a biochemical test for homocysteine levels may provide more useful This is less expensive than having a MTHFR gene test, which in most cases is not covered under the Medicare Benefits Schedule (MBS).

Managing patients who have had MTHFR gene testing

The following points may be useful in a discussion with a patient who has had a MTHFR gene test and is concerned about the results:

  • The presence of one or both MTHFR gene variants (Cys677Thr and/or p.Ala1298Cys) is not associated with particular health problems
    • Individuals who have the MTHFR gene variant(s) might have mildly increased homocysteine levels. While this was once thought to be associated with particular health problems (ie thrombophilia, CVD, recurrent pregnancy loss), recent studies have found that this is not the Many other factors also increase homocysteine (ie diet, lifestyle, other gene variants). A person can reduce their risk of disease by following a healthy, balanced diet and avoiding well-known risk factors such as smoking and overweight.
    • Women who have MTHFR gene variant(s) may have a slightly increased risk of having a baby with neural tube defects (eg spina bifida). However, taking folic acid supplements at standard recommended doses before and during pregnancy decreases the risk, just as it does in women who do not have MTHFR gene variant(s).
  • Genetic services are unlikely to accept referrals for consultations about the results of MTHFR gene testing for these mild variants because the presence of MTHFR gene variants is unlikely to significantly affect a patient’s health.

Further reading

Resources for general practitioners

Resource for general practitioners